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肺肉瘤样癌患者的生物标志物价值:33 例的分子分析。

The value of biomarkers in patients with sarcomatoid carcinoma of the lung: molecular analysis of 33 cases.

机构信息

Department of Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

出版信息

Clin Lung Cancer. 2012 Jul;13(4):288-96. doi: 10.1016/j.cllc.2011.11.004. Epub 2011 Dec 13.

Abstract

UNLABELLED

To better understand the prognosis of sarcomatoid carcinoma of the lung, the correlation between several biomarkers (ERCC1 [excision repair cross-complementation group 1] and EGFR [epidermal growth factor receptor] expression, EGFR and KRAS mutations, and EGFR copy number) and clinical outcomes in 33 patients with lung sarcomatoid carcinoma was evaluated. Survival analysis identified several significant factors that predicted overall survival.

BACKGROUND

Sarcomatoid carcinoma (SC) of the lung is a rare histologic group of lung cancers with a poor prognosis. To better understand the prognosis of lung SC, in this study, we evaluated the correlation between several biomarkers and clinical outcomes in patients with lung SC.

PATIENTS AND METHODS

A cohort of 33 patients with lung SC was studied. Protein expressions of excision repair cross-complementation group 1 (ERCC1) and epidermal growth factor receptor (EGFR) were examined by immunohistochemistry. Somatic EGFR and KRAS mutations were identified by direct sequencing. EGFR gene copy number was evaluated by fluorescence in situ hybridization. ERCC1 messenger RNA expression in paraffin-embedded tumor specimens was detected by branched DNA assay.

RESULTS

Our analyses identified 9 patients (9/32) with EGFR mutations and only 1 patient (1/32) with a KRAS mutation. No exon 19 deletion of EGFR gene was detected. Lower messenger RNA levels of ERCC1 were detected in patients with EGFR mutations and/or fluorescence in situ hybridization amplified status. Survival analysis identified several significant factors, including performance status and clinical staging, that predicted for overall survival.

CONCLUSION

SC exhibits diverse genotypic variations. Results of our study suggest that chemotherapy could still be an optimal solution for untreated advanced SC, whereas EGFR tyrosine kinase domain inhibitors alone may not be an effective approach.

摘要

目的

为了更好地了解肺肉瘤样癌的预后,评估了 33 例肺肉瘤样癌患者的几种生物标志物(ERCC1[切除修复交叉互补组 1]和 EGFR[表皮生长因子受体]表达、EGFR 和 KRAS 突变以及 EGFR 拷贝数)与临床结局的相关性。生存分析确定了几个预测总生存期的显著因素。

背景

肺肉瘤样癌(SC)是一种罕见的肺组织学类型,预后较差。为了更好地了解肺 SC 的预后,在这项研究中,我们评估了几种生物标志物与肺 SC 患者临床结局的相关性。

患者和方法

对 33 例肺 SC 患者进行了队列研究。采用免疫组织化学法检测切除修复交叉互补组 1(ERCC1)和表皮生长因子受体(EGFR)的蛋白表达。通过直接测序鉴定体细胞 EGFR 和 KRAS 突变。通过荧光原位杂交评估 EGFR 基因拷贝数。采用分枝 DNA 法检测石蜡包埋肿瘤标本中 ERCC1 的信使 RNA 表达。

结果

我们的分析确定了 9 例(9/32)患者存在 EGFR 突变,仅有 1 例(1/32)患者存在 KRAS 突变。未检测到 EGFR 基因外显子 19 缺失。存在 EGFR 突变和/或荧光原位杂交扩增状态的患者中 ERCC1 信使 RNA 水平较低。生存分析确定了几个显著因素,包括体能状态和临床分期,这些因素预测了总生存期。

结论

SC 表现出多种基因型变异。我们的研究结果表明,对于未经治疗的晚期 SC,化疗仍然是一种最佳选择,而单独使用 EGFR 酪氨酸激酶结构域抑制剂可能不是一种有效的方法。

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